Classifying interval cancers

doi:10.1016/S0009-9260(05)83218-0

Clinical Radiology

Volume 50, Issue 11, November 1995, Pages 774-777

https://doi.org/10.1016/S0009-9260(05)83218-0 Get rights and content

No definitive way of classifying interval breast cancers (cancers presenting between screening rounds) has been determined, yet their number and classification forms one of the quality assurance (QA) standards for the National Health Service Breast Screening Programme (NHSBSP). This study was undertaken to identify how different screening centres undertake this process, and to compare the classifications obtained when a test set of mammograms was reviewed using three different methods.

A questionnaire was sent to the 17 Regional UK breast screening QA centres. Twelve (80%) of the 15 centres completing the questionnaire had a formal method for reviewing interval cancers. Five of these (33%) attempted to simulate screening by mixing the interval cancers with other screening films. In 11 (73%) centres, a group (size range 3–14) of radiologists was involved.

In a simulated film viewing exercise we assessed whether different methods of classification would alter the number of interval cancers classified as false negative (where an abnormality suspicious of malignancy can be identified on review of the original screening films). Six radiologists reviewed a set of 50 interval cancers by three different methods: independent reading of the interval cancers mixed with screening mammograms; independent reading of the interval cancers on their own; and finally a consensus opinion of the interval cancers alone using the films taken at diagnosis. No discussion or review of these cases had taken place prior to the study.

The number of interval cancers classified as false negative increased by 10% when they were reviewed in isolation compared to review among ‘normal’ screening films. The false negative rate varied widely (4% to 56% P<0.01) depending on the criteria required to fulfil a false negative interval cancer classification—whether only one, a majority, or all of the radiologists were required to see the abnormality on the original screening films.

In order for inter-unit and regional comparisons to be useful, a standard review method of mixing the interval cancer films with normal screening films and using a consensus opinion by a minimum of three external reviewers is suggested.

References (14)

TabarL et al.
Reduction in mortality from breast cancer after mass screening with mammography. Randomised trial from the Breast Cancer Working Group of the Swedish Working Group National Board of Health and Welfare
Lancet
(1985)
VerbeekALM et al.
Reduction on breast cancer mortality through mass screening with modern mammography. First results of the Nijmegen Project, 1975–1981
Lancet
(1984)
ColletteHJ et al.
Evaluation of screening for breast cancer in a non-randomised study (the DOM project) by means of a case-control study
Lancet
(1984)
BuchananJB et al.
Tumour growth, doubling times and the inability of the radiologist to diagnose certain cancers
Radiologic Clinics of North America
(1983)
DayNE et al.
Breast cancer screening programmes: the development of monitoring and evaluation system
British Journal of Cancer
(1989)
FrisellJ et al.
Analysis of interval breast carcinomas in a randomised screening trial in Stockholm
Breast Cancer Research and Treatment
(1987)
PeetersPH et al.
Occurrence of interval cancers in the Nijmegen screening programme
British Journal of Cancer
(1989)

There are more references available in the full text version of this article.

Cited by (37)

Breast screening: What can the interval cancer review teach us? Are we perhaps being a bit too hard on ourselves?
2017, European Journal of Radiology
Citation Excerpt :
False negative (suspicious) (An abnormality is clearly visible and warrants assessment) [4]. The interval cancer review is a valuable educational tool for film readers as well as a quality assurance process, although the process by which it happens differs between centres, causing variations in the incidence of true interval cancers [5]. The aim of this study was to determine the features that make interval cancers apparent on the preceding screening mammogram and to determine whether changes in the ways of performing the interval cancer review will affect the true interval cancer rate.
The aim of this study was to determine the features that make interval cancers apparent on the preceding screening mammogram and determine whether changes in the ways of performing the interval cancer review will affect the true interval cancer rate.
This study was approved by the clinical governance committee. Mammograms of women diagnosed with an interval cancer were included in the study if they had been allocated to either the “suspicious signs” group or “subtle signs” group, during the historic interval cancer review. Three radiologists, individually and blinded to the site of interval cancer, reviewed the mammograms and documented the presence, site, characteristics and classification of any abnormality. Findings were compared with the appearances of the abnormality at the site of subsequent cancer development by a different breast radiologist. The chi-squared test was used in the analysis of the results, seeking associations between recall concordance and cancer mammographic or histological characteristics.
111/590 interval cancers fulfilled the study inclusion criteria.
In 17% of the cases none of the readers identified the relevant abnormality on the screening mammogram. 1/3 readers identified the relevant lesion in 22% of the cases, 2/3 readers in 28% of cases and all 3 readers in 33% of cases. The commonest unanimously recalled abnormality was microcalcification and the most challenging mammographic abnormality to detect was asymmetric density.
We did not find any statistically significant association between recall concordance and time to interval cancer, position of lesion in the breast, breast density or cancer grade.
Even the simple step of performing an independent blinded review of interval cancers reduces the rate of interval cancers classified as missed by up to 39%.
Film reading in the East Midlands Breast Screening Programme - Are we missing opportunities for earlier diagnosis?
2014, Clinical Radiology
Citation Excerpt :
This detailed monitoring of the programme should prospectively translate into fewer FN interval cancers as diagnostic work-up at assessment comes under greater scrutiny. Interval cancer classification involves a degree of subjectivity due to the method of review, the number of readers involved, and tolerances required to agree a radiological categorization.9,10 Combining radiological categories 2 (uncertain) and 3 (suspicious) gives a similar outcome.
To assess whether there are any significant differences in the film-reading histories of interval or screen-detected cancers, and whether this affects stage at diagnosis.
The rates of screen-detected and interval cancers (overall and by radiological categorization) were observed from 268,067 women screened in the East Midlands Breast Screening Programme over 2004–2007 to assess whether there were differences in incidence based on previous film-reading history. Cancers detected at the subsequent screen and film-reading history were analysed to assess whether this affected stage at diagnosis. Analysis undertaken involved cancer detection rates, confidence intervals, and chi-square tests with Monte Carlo simulation.
Rates of interval cancers were similar in all groups where at least one reader had indicated recall to assessment (6.1–7.7/1000) and were significantly higher in comparison to women whose previous film-reading outcome was unanimous routine rescreen (2.9/1000; p < 0.001). Four point one percent of interval cancers with no previous recall outcomes were false negatives, which was significantly lower compared to the groups where at least one reader had indicated recall (10.9%; p = 0.005). Cancers detected at the subsequent screen demonstrated no significant difference in prognosis dependent on previous film-reading history (p = 0.503).
The prognosis of screen-detected cancers was similar and few cancers were false negatives regardless of film-reading history at the previous screen.
Interval breast cancers: Absolute and proportional incidence and blinded review in a community mammographic screening program
2014, European Journal of Radiology
To evaluate the performance of the first years since the beginning of a mammographic population-based screening program.
Women aged 49–69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared.
A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p = 0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25%, 7/28) was higher than that for true ICs (10%, 7/71), although all these differences were not significant (p ≥ 0.480).
These results showed the possibility to comply with European Community standards in the first years of a screening program implementation.
Interval Breast Cancer
2009, The Breast: Comprehensive Management of Benign and Malignant Diseases
Interval breast cancers in screening: The effect of mammography review method on classification
2007, Breast
Citation Excerpt :
The ‘MS’ category is not strictly considered a ‘missed’ cancer because the mammography findings are subtle and may not have prompted recall from screening, and it is possible that these cancers are largely identified only with knowledge of the subsequently detected IC.6 A few studies have explored the effect of mammography review methodology on classification of IC7–11 and different review methodologies are currently employed, which does not allow valid comparisons within or between programs.6 Optimal review processes are not defined in the European or UK guidelines, although, depending on the adopted method, the reviewer may be facilitated to identify the IC in the screening mammogram, thus review methods will impact classification of the IC.6
Surveillance of interval cancers (IC) lacks standardisation of review methodologies. We investigated the extent to which ‘informed’ or ‘blinded’ review may affect IC classification. This is a retrospective study of 100 validated screening mammograms (20 IC, 80 negative screens) independently reviewed by six radiologists. Three sequenced review methods with increasing information were used: (1) blinded (no IC information, case mix), (2) partially informed, and (3) fully informed. IC ‘screening error’ (SE) reports averaged 24% (10–40), 33% (20–55), and 42% (35–50) for phases 1, 2, and 3, while ‘minimal signs’ (MS) reports averaged 6% (5–15), 10% (10–20), and 20% (15–30), respectively. Negative mammograms classification was MS in 18% (7–39) or SE in 19% (11–29), respectively. MS or SE classification was more likely for method 2 (OR=1.78, p=0.033) and method 3 (OR=3.91, p=0.000) relative to method 1, but no reader effect was evident. Inter-observer agreement in classifying at method 1 was slight (k 0.20), lowest (k 0.06) for MS, and fair (k 0.25) for negative and SE categories. More ‘informed’ review is more likely to yield an IC classification as MS or SE. Due to expected variability, review methods need standardisation to improve screening quality. Our data support blinded review of IC in mammography screening.
Radiological surveillance of interval breast cancers in screening programmes
2006, Lancet Oncology
Citation Excerpt :
Figure 2 shows examples of false-negative and true interval cancers. Standardisation of the classification of interval breast cancers can be difficult because it is affected by the methodology of the review process13,16–22 and is inherently subjective. Three factors are especially important.15–22
Interval breast cancers—those diagnosed after a negative mammographic screen and before the next scheduled screen—are an important indicator of the potential effectiveness of population screening for breast cancer. Although the incidence of interval cancers is usually monitored, radiological surveillance is not undertaken routinely in most screening programmes. Here, we describe radiological surveillance of interval breast cancers and discuss methodological difficulties in the radiological review process and in the categorisation of interval cancers as false-negative, true, or occult. Furthermore, we identify methods that affect whether an interval cancer is classified as a false-negative (missed) or a true interval cancer. For all radiological categories of interval cancers, we outline possible changes to screening programmes that might improve cancer detection. Standardised radiological surveillance of interval cancers might allow within-programme comparisons and has the potential to guide practice and improve quality.

View all citing articles on Scopus

View full text

Classifying interval cancers

Lancet

Lancet

Lancet

Radiologic Clinics of North America

Breast cancer screening programmes: the development of monitoring and evaluation system

British Journal of Cancer

Analysis of interval breast carcinomas in a randomised screening trial in Stockholm

Breast Cancer Research and Treatment

Occurrence of interval cancers in the Nijmegen screening programme

British Journal of Cancer